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Single Cell RNA Sequencing Reveals Differential Cell Cycle Activity In Key Cell Populations During Nephrogenesis

Abha S. Bais, Débora M. Cerqueira, Andrew Clugston, Jacqueline Ho, Dennis Kostka

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ABSTRACTThe kidney is a complex organ composed of more than 30 terminally differentiated cell types that all are required to perform its numerous homeostatic functions. Defects in kidney development are a significant cause of chronic kidney disease in children, which can lead to kidney failure that can only be treated by transplant or dialysis. A better understanding of molecular mechanisms that drive kidney development is important for designing strategies to enhance renal repair and regeneration. In this study, we profiled gene expression in the developing mouse kidney at embryonic day 14.5 at single cell resolution. Consistent with previous studies, clusters with distinct transcriptional signatures clearly identify major compartments and cell types of the developing kidney. Cell cycle activity distinguishes between the “primed” and “self-renewing” sub-populations of nephron progenitors, with increased expression of the cell cycle related genesBirc5, Cdca3, Smc2andSmc4in “primed” nephron progenitors. AugmentedBirc5expression was also detected in immature distal tubules and a sub-set of ureteric bud cells, suggesting thatBirc5might be a novel key molecule required for early events of nephron patterning and tubular fusion between the distal nephron and the collecting duct epithelia.